tbuckley/cabot-search huggingface dataset:
Associations Between Modifiable Risk Factors and Changes in Glycemic Status Among Individuals With Prediabetes
Authors: Salma Nabila, Ji-Eun Kim, Jaesung Choi, JooYong Park, Aesun Shin, Sang-Ah Lee, Jong-koo Lee, Daehee Kang, Ji-Yeob Choi
Journal: Diabetes Care (2023)

OBJECTIVE To examine the associations between modifiable risk factors and glycemic status changes in individuals with prediabetes. RESEARCH DESIGN AND METHODS A total of 10,358 individuals with prediabetes defined by their fasting blood glucose and HbA1c levels from the Health Examinees-Gem study were included in the present study. Modifiable factors, including BMI, abdominal obesity, smoking status, physical activity, alcohol consumption, diet quality, hypertension, and dyslipidemia, were examined to determine their associations with changes in glycemic status during follow-up. In addition, modifiable-factor scores were calculated, and their association with changes in glycemic status was also analyzed. RESULTS The median follow-up time for this study was 4 years (range, 1–7 years). BMI ≥25 kg/m2 (adjusted odds ratio [OR] 0.71 [95% CI 0.63–0.79]), abdominal obesity (OR 0.76 [95% CI 0.68–0.86]), heavy drinking (OR 0.74 [95% CI 0.60–0.91]), hypertension (OR 0.71 [95% CI 0.64–0.79]), and dyslipidemia (OR 0.78 [95% CI 0.70–0.85]) were associated with a lower possibility of normoglycemia reversion. BMI ≥25 kg/m2 (OR 1.58 [95% CI 1.29–1.94]), abdominal obesity (OR 1.31 [95% CI 1.11–1.55]), current smoking (OR 1.43 [95% CI 1.07–1.91]), and hypertension (OR 1.26 [95% CI 1.07–1.49]) were associated with a higher probability of type 2 diabetes progression. Having more favorable modifiable factors was also associated with normoglycemia reversion (OR 1.46 [95% CI 1.30–1.64]) and type 2 diabetes progression (OR 0.62 [95% CI 0.49–0.77]). CONCLUSIONS More favorable modifiable factors were related to a higher probability of returning to normoglycemia and a lower probability of progression to type 2 diabetes.
Chimeric antigen receptor T‐cell therapy in multiple myeloma: A comprehensive review of current data and implications for clinical practice
Authors: Rujul H. Parikh, Sagar Lonial
Journal: CA A Cancer Journal for Clinicians (2023)

Abstract Multiple myeloma (MM) is a hematologic malignancy defined by the clonal proliferation of transformed plasma cells. Despite tremendous advances in the treatment paradigm of MM, a cure remains elusive for most patients. Although long‐term disease control can be achieved in a very large number of patients, the acquisition of tumor resistance leads to disease relapse, especially in patients with triple‐class refractory MM (defined as resistance to immunomodulatory agents, proteosome inhibitors, and monoclonal antibodies). There is an unmet need for effective treatment options in these patients. Chimeric antigen receptor (CAR) T‐cell therapy is a novel approach that has demonstrated promising efficacy in the treatment of relapsed, refractory MM (RRMM). These genetically modified cellular therapies have demonstrated deep and durable remissions in other B‐cell malignancies, and current efforts aim to achieve similar results in patients with RRMM. Early studies have demonstrated remarkable response rates with CAR T‐cell therapy in RRMM; however, durable responses with CAR T‐cell therapies in myeloma have yet to be realized. In this comprehensive review, the authors describe the development of CAR T‐cell therapies in myeloma, the outcomes of notable clinical trials, the toxicities and limitations of CAR T‐cell therapies, and the strategies to overcome therapeutic challenges of CAR T cells in the hope of achieving a cure for multiple myeloma.
The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes
Authors: Pablo Montañés-Agudo, Simona Aufiero, Eva N Schepers, Ingeborg van der Made, Lucia Cócera-Ortega, Auriane C Ernault, Stéphane Richard, Diederik W D Kuster, Vincent M Christoffels, Yigal M Pinto, Esther E Creemers
Journal: Cardiovascular Research (2023)

Abstract Aims In the heart, splicing factors orchestrate the functional properties of cardiomyocytes by regulating the alternative splicing of multiple genes. Work in embryonic stem cells has shown that the splicing factor Quaking (QKI) regulates alternative splicing during cardiomyocyte differentiation. However, the relevance and function of QKI in adult cardiomyocytes remains unknown. In this study, we aim to identify the in vivo function of QKI in the adult mouse heart. Methods and results We generated mice with conditional deletion of QKI in cardiomyocytes by the Cre-Lox system. Mice with cardiomyocyte-specific deletion of QKI died during the foetal period (E14.5), without obvious anatomical abnormalities of the heart. Adult mice with tamoxifen-inducible QKI deletion rapidly developed heart failure associated with severe disruption of sarcomeres, already 7 days after knocking out QKI. RNA sequencing revealed that QKI regulates the alternative splicing of more than 1000 genes, including sarcomere and cytoskeletal components, calcium-handling genes, and (post-)transcriptional regulators. Many of these splicing changes corresponded to the loss of muscle-specific isoforms in the heart. Forced overexpression of QKI in cultured neonatal rat ventricular myocytes directed these splicing events in the opposite direction and enhanced contractility of cardiomyocytes. Conclusion Altogether, our findings show that QKI is an important regulator of the muscle-specific alternative splicing program that builds the contractile apparatus of cardiomyocytes.
An Overview of In Vitro Biological Neural Networks for Robot Intelligence
Authors: Zhe Chen, Qian Liang, Zihou Wei, Xie Chen, Qing Shi, Zhiqiang Yu, Tao Sun
Journal: Cyborg and Bionic Systems (2023)

In vitro biological neural networks (BNNs) interconnected with robots, so-called BNN-based neurorobotic systems, can interact with the external world, so that they can present some preliminary intelligent behaviors, including learning, memory, robot control, etc. This work aims to provide a comprehensive overview of the intelligent behaviors presented by the BNN-based neurorobotic systems, with a particular focus on those related to robot intelligence. In this work, we first introduce the necessary biological background to understand the 2 characteristics of the BNNs: nonlinear computing capacity and network plasticity. Then, we describe the typical architecture of the BNN-based neurorobotic systems and outline the mainstream techniques to realize such an architecture from 2 aspects: from robots to BNNs and from BNNs to robots. Next, we separate the intelligent behaviors into 2 parts according to whether they rely solely on the computing capacity (computing capacity-dependent) or depend also on the network plasticity (network plasticity-dependent), which are then expounded respectively, with a focus on those related to the realization of robot intelligence. Finally, the development trends and challenges of the BNN-based neurorobotic systems are discussed.
Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems
Authors: Ang Li, Jennifer La, Sarah B. May, Danielle Guffey, Wilson L. da Costa, Christopher I. Amos, Raka Bandyo, Emily M. Milner, Karen M. Kurian, Daniel C.R. Chen, Nhan V. Do, Carolina Granada, Nimrah Riaz, Mary T. Brophy, Vipul Chitalia, J. Michael Gaziano, David A. Garcia, Marc Carrier, Christopher R. Flowers, Neil A. Zakai, Nathanael R. Fillmore
Journal: Journal of Clinical Oncology (2023)

Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy.
Chemotherapy and Targeted Therapy for Endocrine-Pretreated or Hormone Receptor–Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update
Authors: Beverly Moy, R. Bryan Rumble, Lisa A. Carey
Journal: Journal of Clinical Oncology (2023)

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.
Issue Information
Journal: American Journal of Hematology (2023)

VINITI (All-Russian Institute of Science & Technological Information) • Web of Science ® (Thomson ISI).For submission instructions, subscription and all other information visit: www.wileyonlinelibrary.com/ajh.Wiley's Corporate Citizenship initiative seeks to address the environmental, social, economic, and ethical challenges faced in our business and which are important to our diverse stakeholder groups.Since launching the initiative, we have focused on sharing our content with those in need, enhancing community philanthropy, reducing our carbon impact, creating global guidelines and best practices for paper use, establishing a vendor code of ethics, and engaging our colleagues and other stakeholders in our efforts.Follow our progress at www.
Fludarabine versus cyclophospamide in combination with myeloablative total body irradiation as conditioning for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study from the Acute Leukemia Working Party of the <scp>European Society for Blood and Marrow Transplantation</scp>
Authors: Sebastian Giebel, Myriam Labopin, Thomas Schroeder, Ryszard Swoboda, Johan Maertens, Jean Henri Bourhis, Giovanni Grillo, Urpu Salmenniemi, Inken Hilgendorf, Nicolaus Kröger, Xavier Poiré, Jan J. Cornelissen, Mutlu Arat, Bipin Savani, Alexandros Spyridonidis, Arnon Nagler, Mohamad Mohty
Journal: American Journal of Hematology (2023)

Total body irradiation (TBI) at a dose of 12 Gy combined with cyclophosphamide (CyTBI12Gy) is one of the standard myeloablative regimens for patients with acute myeloid leukemia (AML) treated with allogeneic hematopoietic cell transplantation (allo-HCT). In clinical practice, cyclophosphamide may be substituted with fludarabine (FluTBI12Gy) to reduce toxicity. We retrospectively compared outcomes of CyTBI12Gy with FluTBI12Gy for patients with AML treated in complete remission (CR) with allo-HCT from either a matched sibling or unrelated donor. Of 1684 adults who met inclusion criteria, 109 patients in each group were included in a matched-pair analysis. The cumulative incidence of relapse at 2 years was 25% in the FluTBI12Gy compared to 28% in the CyTBI12Gy group (p = .44) while non-relapse mortality (NRM) was 17% versus 19%, (p = .89) respectively. The rates of leukemia-free survival and overall survival were 65% versus 54% (p = .28) and 70% versus 60.5% (p = .17). Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was significantly lower for FluTBI12Gy than CyTBI12Gy (16% vs. 34%, p = .005), while the incidences of grade 3-4 acute GVHD and chronic GVHD did not differ significantly. The probability of GVHD and relapse-free survival was 49% in the FluTBI12Gy and 41% in the CyTBI12Gy group (p = .17). We conclude that for patients with AML treated with allo-HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2-4 acute GVHD and encouraging survival rates.
Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial
Authors: Yuqin Song, Hervé Tilly, Shinya Rai, Huilai Zhang, Jie Jin, Hideki Goto, Yasuhito Terui, Ho-Jin Shin, Won Seog Kim, Junning Cao, Jifeng Feng, Hyeon Seok Eom, Tae Min Kim, Xavier Cheng-Hong Tsai, Jyh-Pyng Gau, Hideo Koh, Liling Zhang, Yongping Song, Yu Yang, Wei Li, He Huang, Kiyoshi Ando, Jeff P. Sharman, Laurie H. Sehn, Lilian Bu, Xin Wang, Yanwen Jiang, Jamie Hirata, Calvin Lee, Jun Zhu, Koji Izutsu
Journal: Blood (2023)

In the phase 3 POLARIX study in previously untreated diffuse large B-cell lymphoma, polatuzumab vedotin combined with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) significantly improved progression-free survival (PFS) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with similar safety. Patients were randomized 1:1 to 6 cycles of Pola-R-CHP or R-CHOP plus 2 cycles of rituximab alone. For registration of POLARIX in China, consistency of PFS in an Asia subpopulation (defined as ≥50% of the risk reduction in PFS expected in the global population) was evaluated. Overall, 281 patients were analyzed: 160 patients from Asia in the intention-to-treat (ITT) population of the global study and 121 from an ITT China extension cohort. Of these, 141 were randomized to Pola-R-CHP and 140 to R-CHOP. At data cutoff (28 June 2021; median follow-up 24.2 months), PFS met the consistency definition with the global population, and was superior with Pola-R-CHP vs R-CHOP (hazard ratio, 0.64; 95% confidence interval [CI], 0.40-1.03). Two-year PFS was 74.2% (95% CI, 65.7-82.7) and 66.5% (95% CI, 57.3-75.6) with Pola-R-CHP and R-CHOP, respectively. Safety was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 4 adverse events (AEs; 72.9% vs 66.2%, respectively), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to study treatment discontinuation (5.0% vs 7.2%), and any-grade peripheral neuropathy (44.3% vs 50.4%). These findings demonstrate consistent efficacy and safety of Pola-R-CHP vs R-CHOP in the Asia and global populations in POLARIX. This trial was registered at https://clinicaltrials.gov/ct2/home as # NCT03274492.
Monoclonal gammopathy of thrombotic/thrombocytopenic significance
Authors: Adam J. Kanack, Jordan K. Schaefer, Meera Sridharan, Noah P. Splinter, Mindy C. Kohlhagen, Bandana Singh, Silvana B. De Lorenzo, Emily E. Mauch, Maen A. Hussein, Marwan Shaikh, Shaji Kumar, Renren Wen, Demin Wang, David Murray, Anand Padmanabhan
Journal: Blood (2023)
Conserved angio-immune subtypes of the tumor microenvironment predict response to immune checkpoint blockade therapy
Authors: Madhav Subramanian, Ashraf Ul Kabir, Derek Barisas, Karen Krchma, Kyunghee Choi
Journal: Cell Reports Medicine (2023)

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment. However, only a fraction of patients respond to ICB therapy. Accurate prediction of patients to likely respond to ICB would maximize the efficacy of ICB therapy. The tumor microenvironment (TME) dictates tumor progression and therapy outcome. Here, we classify the TME by analyzing the transcriptome from 11,069 cancer patients based on angiogenesis and T cell activity. We find three distinct angio-immune TME subtypes conserved across 30 non-hematological cancers. There is a clear inverse relationship between angiogenesis and anti-tumor immunity in TME. Remarkably, patients displaying TME with low angiogenesis with strong anti-tumor immunity show the most significant responses to ICB therapy in four cancer types. Re-evaluation of the renal cell carcinoma clinical trials provides compelling evidence that the baseline angio-immune state is robustly predictive of ICB responses. This study offers a rationale for incorporating baseline angio-immune scores for future ICB treatment strategies.
Evaluation of a novel ELISA test using synthetic mycolic acid antigens for serodiagnosis of non-tuberculous mycobacterial (NTM) infections
Authors: Julia Bashford, William Flowers, Charles Haworth, Judy Ryan, Anna Cervi, J R Al Dulayymi, Paul S Mason, Ashley Plank, Mark Baird, Andres Floto
Journal: Thorax (2023)

The diagnosis of non-tuberculous mycobacteria (NTM) is a particular challenge in people with cystic fibrosis. Current standard diagnostic approaches rely on serial sputum culture, which is resource demanding, dependent on patient expectoration and may be compromised by excessive decontamination, conventional bacterial overgrowth and masking by concomitant oral and nebulised antibiotics. An alternative rapid, reliable and inexpensive diagnostic method is therefore urgently needed. Serum of patients with Mycobacterium abscessus infection and chronic suppurative lung disease without NTM infection was tested against an array of novel synthetic mycolic acids, identical or similar to natural components of mycobacterial cell walls, and glycopeptidolipid (GPL)-core antigen, which has previously been investigated in Mycobacterium avium pulmonary infection. Diagnostic accuracy of individual antigens and combination of various antigens were calculated. An ELISA using individual trehalose dimycolates and GPL-core antigen was able to effectively distinguish serum from infected and non-infected individuals with a specificity of 88% and a sensitivity of up to 88%, which increased to 88% sensitivity and 93% specificity by combining several antigens in the test. These results suggest synthetic mycolic acid antigens, used individually or in combination with GPL-core antigen could be successfully used to distinguish patients with M. abscessus infection from disease controls.
Towards development of treat to target (T2T) in childhood-onset systemic lupus erythematosus: PReS-endorsed overarching principles and points-to-consider from an international task force
Authors: Eve Mary Dorothy Smith, Amita Aggarwal, Jenny Ainsworth, Eslam Al-Abadi, Tadej Avcin, Lynette Bortey, Jon Burnham, Coziana Ciurtin, Christian M Hedrich, Sylvia Kamphuis, Deborah M Levy, Laura B Lewandowski, Naomi Maxwell, Eric F Morand, Seza Ozen, Clare E Pain, Angelo Ravelli, Claudia Saad Magalhaes, Clarissa A Pilkington, Dieneke Schonenberg-Meinema, Christiaan Scott, Kjell Tullus, Michael William Beresford
Journal: Annals of the Rheumatic Diseases (2023)

Application of 'treat-to-target' (T2T) in childhood-onset systemic lupus erythematosus (cSLE) may improve care and health outcomes. This initiative aimed to harmonise existing evidence and expert opinion regarding T2T for cSLE.
Human-specific duplicate CHRFAM7A gene is associated with more severe osteoarthritis and amplifies pain behaviours
Authors: Alice Courties, Merissa Olmer, Kevin Myers, Phillip Ordoukhanian, Steven R Head, Padmaja Natarajan, Francis Berenbaum, Jérémie Sellam, Martin K Lotz
Journal: Annals of the Rheumatic Diseases (2023)

Objectives CHRFAM7A is a uniquely human fusion gene that functions as a dominant negative regulator of alpha 7 acetylcholine nicotinic receptor (α7nAChR) in vitro. This study determined the impact of CHRFAM7A on α7nAChR agonist responses, osteoarthritis (OA) severity and pain behaviours and investigated mechanisms. Methods Transgenic CHRFAM7A (TgCHRFAM7A) mice were used to determine the impact of CHRFAM7A on knee OA histology, pain severity in OA and other pain models, response to nAchR agonist and IL-1β. Mouse and human cells were used for mechanistic studies. Results Transgenic (Tg) TgCHRFAM7A mice developed more severe structural damage and increased mechanical allodynia than wild type (WT) mice in the destabilisation of medial meniscus model of OA. This was associated with a decreased suppression of inflammation by α7nAchR agonist. TgCHRFAM7A mice displayed a higher basal sensitivity to pain stimuli and increased pain behaviour in the monoiodoacetate and formalin models. Dorsal root ganglia of TgCHRFAM7A mice showed increased macrophage infiltration and expression of the chemokine fractalkine and also had a compromised antinociceptive response to the α7nAchR agonist nicotine. Both native CHRNA7 and CHRFAM7A subunits were expressed in human joint tissues and the CHRFAM7A/CHRNA7 ratio was increased in OA cartilage. Human chondrocytes with two copies of CHRFAM7A had reduced anti-inflammatory responses to nicotine. Conclusion CHRFAM7A is an aggravating factor for OA-associated inflammation and tissue damage and a novel genetic risk factor and therapeutic target for pain.
Inhibition Of the Rho/Rho-Kinase Pathway Reduces In Vitro Adhesion Of Sickle Cell Anemia Eosinophils To Human Endothelial Cells
Authors: Flavia Rubia Pallis, Daiana Morelli Vital, Kleber Yotsumoto Fertrin, Sara T O Saad, Nicola Conran, Fernando Ferreira Costa, Carla Fernanda Franco-Penteado
Journal: Blood (2013)
CMTM6 overexpression confers trastuzumab resistance in HER2-positive breast cancer
Authors: Fei Xing, Hongli Gao, Guanglei Chen, Lisha Sun, Jiayi Sun, Xinbo Qiao, Jinqi Xue, Caigang Liu
Journal: Molecular Cancer (2023)

Abstract Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is characterized by invasive growth, rapid metastasis and chemoresistance. Trastuzumab is an effective treatment for HER2+ breast cancer; however, trastuzumab resistance leads to cancer relapse and metastasis. CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) has been considered as a new immune checkpoint for tumor-induced immunosuppression. The role of CMTM6 in trastuzumab resistance remains unknown. Here, we uncover a role of CMTM6 in trastuzumab-resistant HER2+ breast cancer. CMTM6 expression was upregulated in trastuzumab-resistant HER2+ breast cancer cell. Patients with high CMTM6 expressing HER2+ breast cancer had worse overall and progression-free survival than those with low CMTM6 expression. In vitro, CMTM6 knockdown inhibited the proliferation and migration of HER2+ breast cancer cells, and promoted their apoptosis, while CMTM6 overexpression reversed these effects. CMTM6 and HER2 proteins were co-localized on the surface of breast cancer cells, and CMTM6 silencing reduced HER2 protein levels in breast cancer cells. Co-immunoprecipitation revealed that CMTM6 directly interacted with HER2 in HER2+ breast cancer cells, and CMTM6 overexpression inhibited HER2 ubiquitination. Collectively, these findings highlight that CMTM6 stabilizes HER2 protein, contributing to trastuzumab resistance and implicate CMTM6 as a potential prognostic marker and therapeutic target for overcoming trastuzumab resistance in HER2+ breast cancer.
Initial validation of the Hidradenitis Suppurativa Quality of Life tool in a clinical trial setting
Authors: Leandro L Santos, Zhaoyin Zhu, Kurt Brown, Joslyn S Kirby
Journal: British Journal of Dermatology (2023)

We tested a new patient-reported outcome tool, the Hidradenitis Suppurativa Quality of Life (HiSQoL) questionnaire, which is designed to measure quality of life (QoL) in adults with hidradenitis suppurativa (HS). The HiSQoL demonstrated validity and reliability, and may be a useful tool for measuring QoL, especially in clinical trials testing new drugs in HS.
Clinical application and detection techniques of liquid biopsy in gastric cancer
Authors: Shuo Ma, Meiling Zhou, Yanhua Xu, Xinliang Gu, Mingyuan Zou, Gulinaizhaer Abudushalamu, Yuming Yao, Xiaobo Fan, Guoqiu Wu
Journal: Molecular Cancer (2023)

Abstract Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.